Objective: The aim of this study was to evaluate the effect of
radioactive iodine (RAI) ablation therapy on the complete blood count
(CBC) in thyroid cancer patients.

Materials and Methods: One hundred sixty four patients undergoing
RAI ablation therapy after total thyroidectomy were included. CBC
results were available from the patients' medical records at the
time of ablation and at the 1st, 6th, and 12th months after RAI therapy.

Results: Hemoglobin (Hb), white blood cell (WBC) and platelet (Plt)
values were significantly lower than baseline at 1 month after treatment
(p<0.0001). Hb and WBC values were increased at the 6th month and at
the 1st year. Plt values increased at the 6th month but had decreased
again at the Pt year. The values were usually in normal ranges except in
the patients with low pretreatment Hb and WBC values.

Treatment of differentiated thyroid cancer (DTC) with radioactive
iodine (RAI) is a standard procedure for the ablation of remnant thyroid
tissue following surgery and for the treatment of iodine-avid metastases
(1). Usually, high doses of RAI (100-150 mCi) are used for total
ablation of thyroid remnants. RAI treatments may be repeated especially
in metastatic patients, and this delivers high cumulative doses to
non-thyroid organs. The side effects of RAI treatment may occur in many
areas and organ systems. The most common side effect is a decreased
saliva production, but severe long-term side effects are rare. Other
organ-specific side effects are found in the lacrimal glands, bone
marrow, lungs, and reproductive organs. Incidence of secondary
malignancies and leukemia might increase with higher RAI doses (2), (3).

Bone marrow suppression can arise after RAI treatment (4). There
are many factors that affect the frequency and severity of bone marrow
suppression. These include the prescribed and total cumulative RAI
doses, frequency of treatments and clearance rate of RAI therapy, and
additively, the patient's bone marrow reserve and degree of bone
marrow metastases (2). Although bone marrow suppression with repeated
high-dose RAI treatments is reported (5), (6), changes in the peripheral
complete blood count (CBC) after an initial RAI ablation treatment is
not well defined. Therefore, we retrospectively evaluated the hemoglobin
(Hb), platelet (Plt) and white blood cell (WBC) counts before ablation
and at the 1st month, 6th month and 1St year following initial RAI
ablation treatment.

Materials and Methods

One hundred and sixty-four patients undergoing RAI remnant ablation
therapy after total thyroidectomy were retrospectively evaluated.
Gender, age and demographic characteristics were recorded. The
patient's CBC results were available in the medical records at the
time of ablation and at the 1st and 6th months and 1st year after RAI
therapy. Patients taking any medications known to affect the CBC; having
any hematological conditions; and/or receiving a second dose of RAI
during the first-year follow-up or external beam radiotherapy or
chemotherapy before RAI therapy or within 1 year after ablation were
excluded from the study. None of the patients had bone marrow
metastases, but one patient had pulmonary metastases and seven patients
had lymph node metastases. Levothyroxine (L-T4) and triiodothyronine
(L-T3) treatments were discontinued after 4-6 weeks and 2 weeks,
respectively, and a low-iodine diet for 2 weeks was recommended before
RAI treatment. None of the patients was prepared for RAI ablation with
recombinant human thyroid stimulating hormone (rhTSH). After total
thyroidectomy, RAI remnant ablation treatment with standard-high RAI
doses [3.7-7.4 GBq (100-200 mCi)] was performed in 6-8 weeks. RAI
therapy was administered as follows: 122 patients (74.4%), 37 patients
(22.6%), and 5 patients (3%) received 100 mCi, 125-150 mCi, and 175-200
mCi, respectively. L-T4 treatment was restarted after 48 hours.
Diagnostic imaging with low-dose RAI (2-5 mCi) was performed within 6-12
months. However, no second RAI treatment or radiotherapy was applied
during the one-year follow-up. All blood tests were analyzed with Full
Automated CBC analyzer (Beckman Coulter LH-750). Hb reference values
were 13-17 g/dl and 11.5-16 g/dl for males and females, respectively.
WBC and Plt count reference values were 4.8-10.8 x [10.sup.3]/UL and
130-400 x [10.sup.3]/UL, respectively. Written informed consent was
obtained from the patients.

Statistical Analysis

Data are presented as the mean[+ or -]standard deviation (SD);
medians with ranges are given when appropriate. Continuous variables
were compared using repeated measures variance analysis for changing
over time. Bonferroni test was used for post-hoc analysis. CBC values
between RAI groups were compared by Student's t test. p<0.05 was
considered statistically significant. All statistical analyses were
performed using SPSS version 13.01 for Windows.

Results

The mean age of patients (24 males, 68 females) was 47[+ or -] 13
years (range: 22-81 years). The baseline characteristics of the patients
are presented in Table 1. Median TSH level was 82 mU/L (range: 32-100
mU/L) because of cessation of L-T4 or L-T3 treatments. Hb
(Males/Females), WBC, and Plt values were significantly lower than
baseline at 1 month after treatment (p <0.0001). Hb and WBC values
had increased at the 6th month and 1St year. The decreases in the Hb
levels were not different between the male and female patients.
Similarly, it was observed that neutrophil and lymphocyte counts
decreased equally. Plt values increased at the 6th month, but decreased
again at the 1st year (Table 2, Figure la, b). There was no requirement
of blood transfusion or febrile neutropenia occurrence in any of the
patients. Although all hematological parameters decreased at the 1st
month and for Plt also at the 1st year, the values were usually in
normal ranges except for those patients with low pretreatment Hb and WBC
values. Before treatment, Hb values were low in 21 patients (12.8%, 8
males, 13 females) while WBC values were low in 7 patients (4.3%); no
patients had iron, vitamin B 12 or folate deficiency. The change in Hb
and WBC values is probably related to the disease status or the
medications used before (Table 3). No significant difference in the
decreasing rate was found between patients with low pretreatment and
normal pretreatment Hb and WBC counts. Similarly, there was no
significant difference when comparing patients receiving different doses
of RAI therapy. No complications were observed.

[FIGURE 1a OMITTED]

[FIGURE 1b OMITTED]

Discussion

Bone marrow suppression is a serious and, if not diagnosed,
potentially life-threatening complication of RAI treatment. Transient
leukopenia, anemia and thrombocytopenia may be observed after RAI
administration, but severe cytopenia is usually seen with high doses of
RAI (>600 mCi) (7). The World Health Organization classification is
used for bone marrow suppression after RAI treatment. While mild and
reversible blood count alternations are observed in grade I-II,
persistent severe cytopenia and aplasia or acute myeloid leukemia are
detected in grade III and grade IV, respectively. Although RAI therapy
induces chromosome damage in the lymphocytes, the effect of RAI depends
on lymphocyte phenotype and RAI activity. Natural killer cells are most
sensitive, followed by B lymphocytes and T-helper lymphocytes. However,
these do not result clinically in an immunosuppression (8), (9). Severe
and permanent bone marrow suppression was reported by Benua et al. (10)
in 8 of 59 patients treated with RAI. In the dosimetric evaluations, six
of these eight patients received in excess of 3Gy (300 rads) to the
blood. When using 2Gy (200 rads) to the blood as the upper limit, Von
Nostrand et al. (11) found that mild transient decreases in blood cell
counts were seen in 90% of the patients. We usually applied 100 mCi RAI
and the dose usually did not exceed 2Gy.

Hypothyroid patients have an increased serum creatine and decreased
glomerular filtration rate. Decreased renal clearance results in
increased RAI retention. Therefore, the bone marrow-absorbed dose after
treatment with RAI would be expected to be lower for patients given
rhTSH, which is protective for hypothyroidism and additionally may
reduce the half-life of RAI, than for patients subjected to L-T4
withdrawal (12-14). Molinaro et al. (15) reported recently that RAI
ablation treatment is associated with a decline in WBC and Plt that
persists for at least one year after ablation without differences
between the rhTSH and the L-T4 withdrawal groups. On the other hand,
Rosario et al. (16) demonstrated that the decrease in WBC and platelets
in the first three months was significantly lower in the rhTSH group
than in the L-T4 withdrawal group. This suggests that the transient
effects on the bone marrow may be more of a dose-related phenomenon,
while the late persistent effects are more influenced by individual
susceptibility. In this study, we documented that Hb, WBC, and Plt
counts in the first month were decreased, but did not persist for a long
time. The patients with low pretreatment Hb and WBC values were not more
susceptible to the suppressive effect of the treatment than the patients
having normal values. Although statistically significant, the decreases
in Hb, WBC and Plt were small and without evidence of clinical
importance. Interestingly, Plt counts were slightly decreased at the 1st
year, similar to the observation of Molinaro et al. (15), but different
from their report, we think that the decreased Plt count was probably
associated with the low-dose RAI (2-5 mCi) applied for diagnostic
imaging at 6-12 months. Although CBC values were normal after RAI
treatment, the statistical results showed that RAI doses were important
for bone marrow suppression. Therefore, physicians should be careful
regarding additive or overdoses.

Sublethal radiation doses damage bone marrow cells and may lead to
leukemia. Acute and chronic myeloid leukemia were reported with RAI
treatment, especially in those with bone metastasis. Incidence of
leukemia was increased in the patients who received more than 800 mCi,
were >45 years and were treated within short intervals. Only very
rarely is acute leukemia found in patients receiving a small RAI dose of
<300 mCi (17-19). Similarly, we did not observe the development of an
acute or chronic myeloid leukemia due to RAI treatment within one year.
However, the long-term outcome of RAI therapy may be different from
these results.

In conclusion, we suggest that RAI therapy can be associated with
slight and reversible changes in Hb, WBC and Plt counts; however, it is
a safe treatment modality for ablation without any serious or persistent
hematological side effects.

Conflict of interest

No author of this paper has a conflict of interest, including
specific financial interests, relationships, and/or affiliations
relevant to the subject matter or materials included in this manuscript.